Figure 3.

Role of activated Protein kinase A (PKA) in the excitation-coupling mechanism and cardiac contraction and relaxation. When PKA is activated by β-adrenergic receptors (βAR) signaling it phosphorylates many components increasing intracellular Ca²⁺ such as L-type calcium channel, ryanodine receptor (RyR2), and cardiac myosin binding protein (cMyBP). These phosphorylated components in turn accelerate the kinetics of cross-bridge cycling and the heart contracts faster and stronger. Whereas, phosphorylation of phospholamban (PLB) by PKA increases sarcoplasmic reticulum (SR) Ca²⁺uptake and typically results in enhanced cardiac relaxation. Similarly, PKA phosphorylates troponin I (cTnI), which decreases myofilaments Ca²⁺ sensitivity and accelerates relaxation as well.